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Hypoxia inducible factor 1

Y-X Cao, Z-Q Wang, J-X Kang, K Liu, C-F Zhao, Y-X Guo, B-H Jiao
OBJECTIVE: It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells. MATERIALS AND METHODS: PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1...
March 2018: European Review for Medical and Pharmacological Sciences
Hadas Pahima, Simona Reina, Noa Tadmor, Daniella Dadon-Klein, Anna Shteinfer-Kuzmine, Nathalie M Mazure, Vito De Pinto, Varda Shoshan-Barmatz
The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity...
February 27, 2018: Oncotarget
Marcele F Bastos, Ana Carolina A V Kayano, João Luiz Silva-Filho, João Conrado K Dos-Santos, Carla Judice, Yara C Blanco, Nathaniel Shryock, Michelle K Sercundes, Luana S Ortolan, Carolina Francelin, Juliana A Leite, Rafaella Oliveira, Rosa M Elias, Niels O S Câmara, Stefanie C P Lopes, Letusa Albrecht, Alessandro S Farias, Cristina P Vicente, Claudio C Werneck, Selma Giorgio, Liana Verinaud, Sabrina Epiphanio, Claudio R F Marinho, Pritesh Lalwani, Rogerio Amino, Julio Aliberti, Fabio T M Costa
Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Zhihui Lu, Nana Song, Bo Shen, XiaLian Xu, Yi Fang, Yiqin Shi, Yichun Ning, Jiachang Hu, Yan Dai, Xiaoqiang Ding, Jianzhou Zou, Jie Teng
BACKGROUND: The hepatocyte growth factor (HGF) target pathway plays pivotal renoprotective roles after acute kidney injury (AKI). Syndecan-1 serves as the co-receptor for HGF. Shedding of syndecan-1 is involved in various pathological processes. Thus, we hypothesized that IRI induced syndecan-1 shedding and inhibiting syndecan-1 shedding would protect against kidney injury by potentiating activation of the HGF receptor c-Met. METHODS: Expression of syndecan-1 and its sheddases were observed in kidneys of sham and I/R mice...
March 20, 2018: Transplantation
Kunyuan Wang, Chenxi Duan, Xuejing Zou, Yang Song, Wenwen Li, Lushan Xiao, Jie Peng, Liheng Yao, Qian Long, Li Liu
Mediator complex subunit 15 (MED15) is a coactivator involved in the regulated transcription of RNA polymerase II-dependent genes and serves an oncogenic role in numerous types of cancer. However, the expression and function of MED15 in hepatocellular carcinoma (HCC) remain unknown. In the present study, the aim was to investigate the expression and clinical significance of MED15 in HCC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis revealed that MED15 mRNA and protein levels were significantly upregulated in HCC tissues compared with those in the corresponding adjacent non-tumor liver tissues...
April 2018: Oncology Letters
Li-Qiang Zheng, Shan-Yi Li, Cheng-Xin Li
The aim of the present study was to identify the potential autophagy-related genes and to explore the underlying molecular mechanisms involved in cutaneous squamous cell carcinoma of head and neck (cSCCHN) by bioinformatics analysis. The Gene Expression Omnibus (GEO) series GSE86544 was downloaded from the GEO database. The primary data was generated from cSCCHN with clinical perineural invasion (PNI) and cSCCHN without PNI, and was further analyzed in order to identify differentially expressed genes (DEGs)...
April 2018: Oncology Letters
Meng Zhao, Yahui Liu, Ran Liu, Jin Qi, Yongwang Hou, Jiao Chang, Li Ren
BACKGROUND/AIMS: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11's role in NSCLC and the detailed mechanism behind it. METHODS: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay...
March 10, 2018: Cellular Physiology and Biochemistry
Fu-Chao Yu, Chu-Xiao Yuan, Jia-Yi Tong, Guang-Hao Zhang, Fang-Ping Zhou, Fang Yang
Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is the key factor in oxidative stress and the concomitant inflammation of endothelial cells (ECs). In recent years, the lipid sphingosine-1-phosphate (S1P) has been reported to probably play a central role in inflammatory diseases. However, its role in IH-induced endothelial injury remains uncertain. In this study, we investigated the IH-induced ECs inflammation and apoptosis, as well as the role of S1P in both. First, human umbilical vein endothelial cells (HUVECs) were treated with IH to explore the mechanism of S1P and S1P microbubbles (S1P-MBs) in HUVECs with altered function...
March 16, 2018: Biochemical and Biophysical Research Communications
Hung-Wei Kan, Jung-Hsien Hsieh, Hsiung-Fei Chien, Yea-Huey Lin, Ti-Yen Yeh, Chi-Chao Chao, Sung-Tsang Hsieh
To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy evidenced by reduced capillary luminal area, increased capillary basement membrane thickness, and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves...
March 16, 2018: Disease Models & Mechanisms
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
Suguru Fukushima, Makoto Endo, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Tomoya Matsunobu, Ken-Ichi Kawaguchi, Nokitaka Setsu, Keiichiro IIda, Nobuhiko Yokoyama, Makoto Nakagawa, Kenichiro Yahiro, Yoshinao Oda, Yukihide Iwamoto, Yasuharu Nakashima
[This corrects the article DOI: 10.1371/journal.pone.0178064.].
2018: PloS One
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
Qiongyuan Hu, Jianan Ren, Guanwei Li, Jie Wu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Jieshou Li
Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls...
March 14, 2018: Cell Death & Disease
Yousef Zakharia, Arup Bhattacharya, Youcef M Rustum
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent...
February 13, 2018: Oncotarget
Tomohiro Katagiri, Minoru Kobayashi, Michio Yoshimura, Akiyo Morinibu, Satoshi Itasaka, Masahiro Hiraoka, Hiroshi Harada
Hypoxic and stroma-rich microenvironments, characteristic features of pancreatic cancers, are strongly associated with a poor prognosis. However, whether and how hypoxia increases stromal compartments remain largely unknown. Here, we investigated the potential importance of a master regulator of the cellular adaptive response to hypoxia, hypoxia-inducible factor-1 (HIF-1), in the formation of stroma-rich microenvironments of pancreatic tumors. We found that pancreatic cancer cells secreted more Sonic hedgehog protein (SHH) under hypoxia by upregulating its expression and efficiency of secretion in a HIF-1-dependent manner...
February 13, 2018: Oncotarget
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
Qixiang Zhao, Zhiwei Liu, Bing Huang, Yanliang Yuan, Xiucheng Liu, Hu Zhang, Fan Qiu, Yiqian Zhang, Yufeng Li, Haoran Miao, Hongyan Dong, Zhongming Zhang
The prevention and management of myocardial ischemia/reperfusion (MI/R) injury is an essential part of coronary heart disease surgery and is becoming a major clinical problem in the treatment of ischemic heart disease. Previous studies by our group have demonstrated that pigment epithelium‑derived factor (PEDF) improves cardiac function in rats with acute myocardial infarction and reduces hypoxia‑induced cell injury. However, the protective function and mechanisms underlying the effect of PEDF in MI/R injury remain to be fully understood...
March 9, 2018: International Journal of Molecular Medicine
Antonella Cotoia, Lucia Mirabella, Sabrina Altamura, Rachele Villani, Flavia Marchese, Giuseppe Ferrara, Karim Mariano, Tullo Livio, Gilda Cinnella
BACKGROUND: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments...
March 12, 2018: Trials
Iglika G Ivanova, Catherine V Park, Adrian I Yemm, Niall S Kenneth
HIF1α (hypoxia inducible factor 1α) is the central regulator of the cellular response to low oxygen and its activity is deregulated in multiple human pathologies. Consequently, given the importance of HIF signaling in disease, there is considerable interest in developing strategies to modulate HIF1α activity and down-stream signaling events. In the present study we find that under hypoxic conditions, activation of the PERK branch of the unfolded protein response (UPR) can suppress the levels and activity of HIF1α by preventing efficient HIF1α translation...
February 26, 2018: Nucleic Acids Research
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